Mitoxantrone-Induced Cardiotoxicity in Acute Myeloid Leukemia-A Velocity Vector Imaging Analysis.

BACKGROUND: The purpose of this investigation was to: (1) determine incidence and predictors of mitoxantrone-induced early cardiotoxicity and (2) study left ventricular mechanics before and after receiving mitoxantrone. METHOD AND RESULTS: We retrospectively analyzed 80 subjects diagnosed with acute myeloid leukemia (AML) who underwent chemotherapy with bolus high-dose mitoxantrone. Echocardiographic measurements were taken at baseline and at a median interval of 55 days after receiving mitoxantrone. Thirty-five (44%) of the patients developed clinically defined early cardiotoxicity, 29 (36%) of which developed heart failure. There was a significant decrease in the ejection fraction (EF) not only in the cardiotoxicity group (17.6 ± 14.8%, P < 0.001) but also in the noncardiotoxicity group (5.3 ± 8.4%, P < 0.001). Decrease in global longitudinal strain (GLS) (-3.7 ± 4.5, P < 0.001 vs. -2.4 ± 4.3, P = 0.01) and global circumferential strain (GCS) (-5.6 ± 9, P = 0.003 vs. -5.3 ± 8.7, P < 0.001) was significant in both the cardiotoxicity and noncardiotoxicity group, respectively. A multivariate model including baseline left ventricular end-systolic diameter, baseline pre-E/A ratio, and baseline pre-E/e' ratio was found to be the best-fitted model for prediction of mitoxantrone-induced early clinical cardiotoxicity. CONCLUSION: High-dose mitoxantrone therapy is associated with an excellent remission rate but with a significantly increased risk of clinical and subclinical early cardiotoxicity and heart failure. Mitoxantrone-induced systolic dysfunction is evident from reduction in EF, increase in Tei index, and significant reduction in GLS and GCS. Baseline impaired ventricular relaxation evident from higher E/e' ratio and lower E/A ratio independently predicts increased risk of mitoxantrone-induced early cardiotoxicity.

Systolic pulmonary and hepatic vein flow reversal due to pacemaker-induced retrograde ventriculoatrial conduction.

Systolic pulmonary and hepatic vein flow reversals can typically be seen with severe atrioventricular (AV) valve regurgitation and during atrial fibrillation (AF). We report the case of a 67-year-old woman who presented with recent-onset exertional dyspnea. Her pacemaker was near end-of-life and reverted to a VVI mode from the preset DDDR mode. Electrocardiography demonstrated retrograde 1:1 ventriculoatrial (VA) conduction and spectral Doppler analysis revealed prominent systolic pulmonary and hepatic vein flow reversals. Symptoms, electrocardiogram (ECG) findings, and the spectral Doppler abnormalities resolved completely following a generator replacement and resumption of DDDR pacing.

Speckle echocardiographic left atrial strain and stiffness index as predictors of maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study.

BACKGROUND: Echocardiographic left atrial (LA) strain parameters have been associated with atrial fibrillation (AF) in prior studies. Our goal was to determine if strain measures [peak systolic longitudinal strain (LAS) and stiffness index (LASt)] changed after cardioversion (CV); and their relation to AF recurrence. METHODS AND RESULTS: 46 participants with persistent AF and 41 age-matched participants with no AF were recruited. LAS and LASt were measured before and immediately after CV using 2D speckle tracking imaging (2DSI). Maintenance of sinus rhythm was assessed over a 6-month follow up. Mean LAS was lower, and mean LASt higher, in participants with AF before CV as compared to control group (11.9±1.0 vs 35.7±1.7, p<0.01 and 1.31±0.17 vs 0.23±0.01, p<0.01, respectively). There was an increase in the mean LAS immediately after CV (11.9±1.0 vs 15.9±1.3, p<0.01), whereas mean LASt did not change significantly after CV (p=0.62). Although neither LAS nor LASt were independently associated with AF recurrence during the follow-up period, change in LAS after cardioversion (post-CV LAS-pre-CV LAS) was significantly higher among individuals who remained in sinus rhythm when compared to individuals with recurrent AF (3.6±1.1 vs 0.4±0.8, p=0.02). CONCLUSIONS: LAS and LASt differed between participants with and without AF, irrespective of the rhythm at the time of echocardiographic assessment. Baseline LAS and LASt were not associated with AF recurrence. However, change in LAS after CV may be a useful predictor of recurrent arrhythmia.

Chemotherapy-induced cardiotoxicity.

Anthracycline-based chemotherapeutics have long been recognized as effective agents for treating a wide range of malignancies. However, their use is not without significant adverse cardiotoxic side effects. Strategies for prevention involve limiting free-radical production and subsequent cardiac myocyte damage. Dexrazoxane remains the most widely studied cardioprotective medication. Alternative agents may reduce cardiotoxicity but may still cause significant cardiovascular problems. The role of ß-blockers and angiotensin-converting enzyme inhibitors in the treatment of heart failure is well proven. The role of these medications in the prevention and treatment of chemotherapy-induced cardiotoxicity is not well established.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF.

Relation of Atrial Fibrillation in Acute Myocardial Infarction to In-Hospital Complications and Early Hospital Readmission.

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) and contributes to high rates of in-hospital adverse events. However, there are few contemporary studies examining rates of AF in the contemporary era of AMI or the impact of new-onset AF on key in-hospital and postdischarge outcomes. We examined trends in AF in 6,384 residents of Worcester, Massachusetts, who were hospitalized with confirmed AMI during 7 biennial periods between 1999 and 2011. Multivariate logistic regression analysis was used to examine associations between occurrence of AF and various in-hospital and postdischarge complications. The overall incidence of AF complicating AMI was 10.8%. Rates of new-onset AF increased from 1999 to 2003 (9.8% to 13.2%), and decreased thereafter. In multivariable adjusted models, patients developing new-onset AF after AMI were at a higher risk for in-hospital stroke (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.6 to 4.1), heart failure (OR 2.0, 95% CI 1.7 to 2.4), cardiogenic shock (OR 3.7, 95% CI 2.8 to 4.9), and death (OR 2.3, 95% CI 1.9 to 3.0) than patients without AF. Development of AF during hospitalization for AMI was associated with higher rates of readmission within 30 days after discharge (21.7% vs 16.0%), but no significant difference was noted in early postdischarge 30-day all-cause mortality rates (8.3% vs 5.1%). In conclusion, new-onset AF after AMI is strongly related to in-hospital complications of AMI and higher short-term readmission rates.

Atrial Fibrillation and Hypertension: Mechanistic, Epidemiologic, and Treatment Parallels.

Atrial fibrillation (AF) is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and hypertension (HTN). Of all the risk factors, HTN is the most commonly encountered condition in patients with incident AF. Hypertension is associated with a 1.8-fold increase in the risk of developing new-onset AF and a 1.5-fold increase in the risk of progression to permanent AF. Hypertension predisposes to cardiac structural changes that influence the development of AF such as atrial remodeling. The renin angiotensin aldosterone system has been demonstrated to be a common mechanistic link in the pathogenesis of HTN and AF. Importantly, HTN is one of the few modifiable AF risk factors, and guideline-directed management of HTN may reduce the incidence of AF.

Predictors of ascending aortic dilation in bicuspid aortic valve disease: a five-year prospective study.

BACKGROUND: Bicuspid aortic valves are associated with aortic dilation and dissection. There is a paucity of prospective studies evaluating changes in aortic size over time in adult subjects with bicuspid aortic valves. METHODS: A total of 115 subjects with asymptomatic bicuspid aortic valves were enrolled from 2003 to 2008 and followed prospectively over 5 years. Clinical and family histories, as well as transthoracic echocardiograms, were obtained at baseline, and echocardiograms were performed annually thereafter. RESULTS: The mean age of subjects was 41.8 ± 12.8 years, and 61% were male. Ascending aortic size at baseline averaged 35.5 ± 5.6 mm and increased in 71.1% of subjects (mean, 0.66 ± 0.05 mm/y; range, 0.2-2.3 mm/y) over an average of 4.8 years. In 15.6% of subjects, the rate of change exceeded 1 mm/y. The average rate of ascending aortic dilation for all subjects was 0.47 ± 0.05 mm/y (P < .001). A family history of aortic valve disease was associated with progression in both unadjusted (P = .029) and logistic regression analyses adjusted for age, gender, and body surface area (odds ratio, 13.7; P = .021). Multivariate analysis did not find leaflet orientation or moderate to severe aortic valve dysfunction as independent predictors of aortic dilation. CONCLUSIONS: We found that in subjects with bicuspid aortic valve, studied prospectively, there was an annual rate of ascending aortic dilation of 0.47 mm/y. In contrast to previous reports, leaflet orientation and aortic valve dysfunction were not independent predictors of aortic dilation. A family history of aortic valve disease was associated with a significantly increased risk of increasing ascending aortic size.

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

INTRODUCTION: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. METHODS: One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI (>3 months post-PVI) over the 6-month follow-up period. RESULTS: A BNP greater than or equal to 100 pg/dL (P=0.01) and AF recurrence within 3 months after PVI (P<0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P=0.001) and a net reclassification improvement of 60% (P=0.001) for all risk scores. CONCLUSIONS: Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence.

Stroke and Death Prediction with the Impact of Vascular Disease in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia encountered in the U.S. and the growing burden of AF has profound health implications due to the association of AF with an increased risk of stroke, heart failure, and mortality. AF is a significant risk factor for thromboembolic stroke; and also independently increases total mortality in patients with and without cardiovascular disease. Various risk stratification schemes such as CHADS2 and CHA2DS2-VASc have been implemented in clinical practice to determine the risk of cardio-embolic stroke, and need for thrombo-prophylaxis in patients with AF. AF is also closely related to the pathophysiology of other cardiovascular and peripheral vascular disease. Many patients with AF have associated atherosclerosis given that many risk factors for atherosclerosis also predispose to AF. Myocardial infarction (MI) is also closely related to AF and its clinical course is affected by new onset AF. This review elucidates the impact of AF on major adverse cardiovascular events and mortality outcomes in relation to stroke, coronary artery disease and peripheral vascular disease.

Apixaban in patients with Atrial Fibrillation: A Systematic Review.

Atrial fibrillation (AF) is the most common cardiac arrhythmia which increases the risk of stroke and systemic embolism by 5- fold, it is a major global public health problem. Stroke is associated with greatest mortality and morbidity in patients with AF. Strokes associated with AF are especially large and disabling, and consequently primary prevention is paramount. Antithrombotic therapy is the mainstay of stroke prevention. Vitamin K antagonists (VKA's) have been the standard anticoagulants in stroke prophylaxis for patients with AF for decades. Despite their effectiveness, they are limited by several factors such as narrow therapeutic index, drug- drug interactions, slow onset and offset of action, hemorrhage and routine anticoagulation monitoring to maintain therapeutic international normalized ratio (INR). During recent times, various novel anticoagulants have been developed to expand the therapeutic option for stroke prevention. Apixaban is a novel oral anticoagulant which has been developed and clinically investigated for prevention of stroke in AF patients. This review discusses the pharmacological properties, results of clinical trials investigating role of apixaban for prevention of stroke and its future potential in clinical practice.

Newer anticoagulants in cardiovascular disease: a systematic review of the literature.

Vitamin K antagonists (VKAs) such as warfarin have traditionally been the major therapeutic option for anticoagulation in clinical practice. VKAs are effective and extensively recommended for the prevention of venous and arterial thromboembolism in cardiovascular disease. Despite its effectiveness, warfarin is limited by factors such as a narrow therapeutic index, drug-drug interactions, food interactions, slow onset and offset of action, hemorrhage, and routine anticoagulation monitoring to maintain therapeutic international normalized ratio. During the last 2 decades, the approval of anticoagulants, such as low-molecular-weight heparins, indirect factor Xa inhibitors (eg, fondaparinux), and direct thrombin inhibitors (eg, argatroban, lepirudin, and desirudin), have expanded the number of available antithrombotic compounds with additional targets within the anticoagulation pathway. Although these medications offer several potential therapeutic advantages, they all require parenteral or subcutaneous administration and are substantially more expensive than VKAs. Thus, VKAs, despite several limitations, have remained the major option for most patients requiring chronic anticoagulation. These limitations have prompted interest in the development of newer oral anticoagulants. Novel anticoagulants targeting inhibition of factor Xa and thrombin (factor IIa) have now been incorporated into clinical practice based on the results of large randomized clinical trials, with the recent U.S. Food and Drug Administration approval of dabigatran for stroke prevention in atrial fibrillation and rivaroxaban for deep vein thrombosis and stroke prevention in atrial fibrillation, with multiple other agents in various stages of development for these and other indications. This review discusses the pharmacological properties, clinical results, and therapeutic applications of novel and new anticoagulants, thereby providing an outline for the future of anticoagulation in cardiovascular disease.

Management strategies in atrial fibrillation in patients with heart failure.

Atrial fibrillation (AF) and heart failure (HF) frequently occur together, and their coexistence is associated with a poor prognosis. AF and HF share risk factors, but their relationship involves complex hemodynamic, neurohormonal, inflammatory, ultrastructural, and electrophysiologic processes that extend beyond epidemiological associations. The shared mechanisms underlying AF and HF have important implications for the treatment of AF in patients with HF. This article focuses on reviewing contemporary data as it pertains to AF management in patients with HF and provides insight into investigational therapies currently under development.

Atrial fibrillation and heart failure parallels: lessons for atrial fibrillation prevention.

Heart failure (HF) and atrial fibrillation (AF) are 2 of the most common cardiovascular diseases encountered in clinical practice, and the prevalence of these diseases continues to grow worldwide with the aging of the global population. While recognizing that AF is a heterogeneous disorder, we submit that the parallels between AF and HF may arise because many cases of AF and HF result from the cumulative exposure of the atria and ventricles to a common set of systemic cardiovascular risk factors. Over time, exposure to risk factors promotes development of atrial and ventricular structural and functional abnormalities through activation of several biologic pathways in concert: upregulation of neurohormonal signaling cascades, release of inflammatory mediators, programmed cell death, and fibrosis. Cardiac structural remodeling occurs in concert with electrophysiologic remodeling, both of which contribute to atrial and ventricular rhythm disturbances, including AF. AF and HF, instead of representing distinct disease processes, often represent different endpoints along a disease continuum. By reviewing some of the mechanistic parallels between AF and HF, we hope to emphasize the connection between established cardiovascular risk factors, cardiac remodeling and AF, with a view to promote strategies for AF prevention.

Complications from catheter ablation of atrial fibrillation: a systematic review.

Atrial fibrillation (AF) is the most common arrhythmia requiring treatment that is encountered in clinical practice. Recent advances in the understanding of underlying mechanisms of AF have led to the increased use of catheter ablation (CA) as a treatment modality for paroxysmal, persistent, or long-standing persistent AF in patients with symptomatic AF despite treatment with antiarrhythmic medications. Because of the complexity in technique and anatomic location of the ablation sites, it is not surprising that CA of AF is associated with a greater risk of procedural complications compared with simpler cardiac ablation procedures. Major and minor complications, including life-threatening complications, have been described and quantified. This systematic review describes the potential risks of CA that have been reported over a period and provides insights into the evolving strategies to minimize these complications, thus making CA techniques safer and potentially more efficacious for AF.